Currently, there are no biomarkers to predict the drug response, and the mechanisms of resistance are poorly characterised in HNSCC.40,43 In a recent time, course study to investigate the transcriptional and DNA methylation signatures driving acquired cetuximab resistance in HNSCC, we found that an essential driver of resistance to anti-EGFR-targeted therapies, FGFR1, is epigenetically regulated during chronic exposure to cetuximab and provide strong evidence that epigenetic alterations can drive acquired resistance.10 The gene discussed is EGFR; the disease is head and neck squamous cell carcinoma.